The enormous, even exponential, advance in the understanding of human genetics over the past three decades has so far yielded much less improvement in clinical results than was once hoped. It has proved more difficult than anticipated to translate biological knowledge into clinical benefit.

This is not, of course, to say that there have been no benefits at all from the advances in genetic understanding, particularly in such fields as prenatal counselling. Another superficially promising field is that of pharmacogenetics, that is to say the prediction of responses to medicaments according to the patients’ genetic type. This is very important, for hitherto it has proved difficult to predict whether a patient will respond positively or negatively to a given treatment, and whether he or she needs a higher or a lower dose to produce a desired effect.

The latter is particularly important in the case of treatment with anticoagulants (blood-thinners) because a therapeutic dose is usually so close to a dangerous dose. If we could predict who needs what dose rather than, as at present, proceed essentially by trial and error, it would be of great advantage to patients who need anticoagulation. They would receive the benefit of anticoagulation – fewer heart attacks and strokes – without the risks of complications such as cerebral and other bleeds.

Three trials of attempts to tailor doses of anticoagulants according to the patients’ genetic type have been published in a recent edition of the New England Journal of Medicine. The authors compared prescription of anticoagulants by the normal methods with determination by genetic type. The results of the three trials were contradictory.

It's also like the difference between deciphering a lost language, and being able to compose a major piece of literature in that language. It may be that we finally possess most of the building blocks & knowledge needed to make clinical genetic breakthroughs. But we had the necessary tools & knowledge to invent antibiotics for centuries, and the actual breakthrough still had to wait for the right genius at the right place & time.

We may have many tools, but we certainly don't have enough knowlege. The interaction of genes with other genes, proteins, and other substances is very complicated. Furthermore there are developmental factors involved. Think of thalidomide. One genius will not be able to come up with a simple answer. Thousands of scientists will spend their lifetime elucidating small bits of the enormous complexity of living beings.

But the analogy with antibiotics is flawed. They have quite predictably and reliably destroyed things that make people sick and kill them, thus making them well. Once the bacterial causes were known, the only thing needed was a bacteria killer for certain ones. Everything is highly deterministic cause/effect. We know that genes exist but we still theorizing about what they do and how and what they might cause. I fail too see any interesting analogy with antibiotics.

So our main successes so far are in prenatal counseling? And that is because success consists in talking and possible abortion, where "success" has nothing to do with genetics? So genetics here is successful as long as success can mean failure. Got it.

Look, "genetic predispositions" may not be predispositions at all. Philosophically predispositions in anything are highly problematic concepts. Genetic predispositions may be nothing like the common sense understanding of predispositions as we understand it in any other area, say ease in picking up a second language or some such. It might well be the whole genetic predisposition business in a category error. And would it be that surprising? These are the folks who began their field in the crucible of the Eugenics movement and were entirely discredited, but not by peer review, but by the social recoil from Hitler and the Nazis taking these beliefs on a wider scale. It wouldn't be thT surprising if in a couple of decades there is no more predictive power in genetics than now. But don't hold your breath for the soul searching if that happens, but instead expect a raft of theories trying to account for the failures and the immenent success that is always just around the corner.

It's a little like asking why it's hard to get to the moon, I mean there it is in clear sight and all. The short answer is that it's because, even when you understand it thoroughly, it remains difficult.

The depth of our understanding of anything genomic at the moment is still modest, and we don't even know how modest. OTOH genetics is already having tremendous effects on practice in breast cancer and some other areas, and would have a lot more if the pharms weren't against it and the physicians hobbled by this "practice" model which is pre-scientific. AFAIK this is still how medicine is taught. Maybe it still has to be, our science just isn't yet really better than our voodoo in too many cases.

Eventually the science will win, but it could be a couple of generations of both scientific progress and educational reform.